Соціальний капітал у формуванні екстерналій освітньої сфери

У статті аналізується передавальний механізм імпульсу, який одержує економіка від зміни рівня освіти. Виходячи із припущення про прискорення (уповільнення) економічного зростання як одну із можливих екстерналій освіти, автори досліджують опосередкований вплив соціального капіталу на формування цієї екстерналії.В статье анализируется передаточный механизм импульса, полученного экономикой от изменения уровня образования. Исходя из предположения об ускорении (замедлении) экономического роста как о возможной экстерналии образования, авторы исследуют опосредованное влияние социального капитала на формирование этой экстерналии.The article under consideration analyzes the intermediary mechanism of impulse which results in economics due to education level change. In terms of assumption as regards economic growth acceleration (impairment) as one of possible education externalities the authors are researching the indirect social capital influence upon this externality formation

Expression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patients

CITATION: Lubbers, R. et al. 2020. Expression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patients. Molecular Immunology, 120:187–195, doi:10.1016/j.molimm.2020.02.006.The original publication is available at https://www.sciencedirect.comBackground To facilitate better discrimination between patients with active tuberculosis (TB) and latent TB infection (LTBI), whole blood transcriptomic studies have been performed to identify novel candidate host biomarkers. SERPING1, which encodes C1-inhibitor (C1-INH), the natural inhibitor of the C1-complex has emerged as candidate biomarker. Here we collated and analysed SERPING1 expression data and subsequently determined C1-INH protein levels in four cohorts of patients with TB. Methods SERPING1 expression data were extracted from online deposited datasets. C1-INH protein levels were determined by ELISA in sera from individuals with active TB, LTBI as well as other disease controls in geographically diverse cohorts. Findings SERPING1 expression was increased in patients with active TB compared to healthy controls (8/11 cohorts), LTBI (13/14 cohorts) and patients with other (non-TB) lung-diseases (7/7 cohorts). Serum levels of C1-INH were significantly increased in The Gambia and Italy in patients with active TB relative to the endemic controls but not in South Africa or Korea. In the largest cohort (n = 50), with samples collected longitudinally, normalization of C1-INH levels following successful TB treatment was observed. This cohort, also showed the most abundant increase in C1-INH, and a positive correlation between C1q and C1-INH levels. Combined presence of increased levels of both C1q and C1-INH had high specificity for active TB (96 %) but only very modest sensitivity 38 % compared to the endemic controls. Interpretation SERPING1 transcript expression is increased in TB patients, while serum protein levels of C1-INH were increased in half of the cohorts analysed.Publisher's versio

Complement Component C1q as Serum Biomarker to Detect Active Tuberculosis.

Background: Tuberculosis (TB) remains a major threat to global health. Currently, diagnosis of active TB is hampered by the lack of specific biomarkers that discriminate active TB disease from other (lung) diseases or latent TB infection (LTBI). Integrated human gene expression results have shown that genes encoding complement components, in particular different C1q chains, were expressed at higher levels in active TB compared to LTBI. Methods: C1q protein levels were determined using ELISA in sera from patients, from geographically distinct populations, with active TB, LTBI as well as disease controls. Results: Serum levels of C1q were increased in active TB compared to LTBI in four independent cohorts with an AUC of 0.77 [0.70; 0.83]. After 6 months of TB treatment, levels of C1q were similar to those of endemic controls, indicating an association with disease rather than individual genetic predisposition. Importantly, C1q levels in sera of TB patients were significantly higher as compared to patients with sarcoidosis or pneumonia, clinically important differential diagnoses. Moreover, exposure to other mycobacteria, such as Mycobacterium leprae (leprosy patients) or BCG (vaccinees) did not result in elevated levels of serum C1q. In agreement with the human data, in non-human primates challenged with Mycobacterium tuberculosis, increased serum C1q levels were detected in animals that developed progressive disease, not in those that controlled the infection. Conclusions: In summary, C1q levels are elevated in patients with active TB compared to LTBI in four independent cohorts. Furthermore, C1q levels from patients with TB were also elevated compared to patients with sarcoidosis, leprosy and pneumonia. Additionally, also in NHP we observed increased C1q levels in animals with active progressive TB, both in serum and in broncho-alveolar lavage. Therefore, we propose that the addition of C1q to current biomarker panels may provide added value in the diagnosis of active TB

Twelve years of pneumococcal conjugate vaccination in the Netherlands: Impact on incidence and clinical outcomes of invasive pneumococcal disease

Introduction: In 2006, the Netherlands introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in their national immunisation programme. In 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). We report on the impact of PCV on invasive pneumococcal disease (IPD) incidence, clinical syndromes and patient outcomes. Methods: Pneumococcal isolates of hospitalised IPD patients between June 2004 and May 2018 were obtained from nine sentinel laboratories, covering 25% of the Dutch population. All isolates were serotyped. IPD incidence and clinical outcome were determined before and after introduction of PCV7 and after the switch to PCV10, stratified by age and serotype. Results: Compared to before PCV7 introduction, significant declines in IPD incidence were observed in 2016–2018 in children <5 years (69%), 18–49 year olds (31%) and ≥65 year olds (19%). Compared to before PCV10 introduction, the IPD incidence in 2016–2018 declined in children <5 years (RR:0.68, 95%CI:0.42–1.11), 5–17 year olds (RR:0.58, 95%CI:0.29–1.14) and 18–49 year olds (RR:0.72, 95%CI:0.57–0.90), but not in 50–64 year olds (RR:0.94, 95%CI:0.81–1.10) and ≥65 year olds (RR:1.04, 95%CI:0.0.93–1.15). While the case fatality rate (CFR) decreased from 16.2% pre-PCV to 13.4% post-PCV10 (RR:0.83, 95%CI:0.70–0.99), the switch to PCV10 had no further impact on CFR (RR:1.14, 95%CI:0.96–1.36). Conclusion: Twelve years of PCV in the Netherlands has resulted in a sustained reduction of IPD incidence in children and younger adults. The switch from PCV7 to PCV10 did not have additional impact on the IPD incidence in older adults and CFR due to emerging non-vaccine serotypes

The extent of microbiological testing is associated with alteration of antibiotic therapy in adults with community-acquired pneumonia

The aim of this study was to explore the relationship between the extent of microbiological testing and the frequency of antibiotic alteration in adults hospitalised with community-acquired pneumonia (CAP). We retrospectively studied 283 immunocompetent patients hospitalised with CAP. Information on microbiological testing and prescribed antibiotics was obtained. Patients were grouped according to the number of different microbiological tests performed within the first 2 days of admission (0-5 tests). Alteration rates were compared between these groups. Antimicrobial alteration was defined as a switch at day 3 of hospital stay to (1) a narrower spectrum antibiotics, or (2) a different class of antibiotics, or (3) a switch from dual therapy to monotherapy (4) or discontinuation of antibiotic treatment because the indication for antibiotic treatment did no longer exist. For each additional test performed, a stepwise increase in percentage of patients with altered antibiotic regimen ranging from 0 to 59% (p = 0.001) was found. Multivariate logistic regression analyses showed that performing PCR assay for atypical pathogens was most strongly associated with any alteration of antibiotic treatment (OR 2.6 (95% CI 1.4-4.9)) and with changes in atypical coverage specifically (OR 3.1 (95% CI 1.6-6.0). The extent of microbiological testing was positively associated with antibiotic alteration in adults hospitalised with CAP. Antibiotic treatment was most likely to be altered in patients in whom PCR assay for atypical pathogens was performed

Twelve years of pneumococcal conjugate vaccination in the Netherlands: Impact on incidence and clinical outcomes of invasive pneumococcal disease

Introduction: In 2006, the Netherlands introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in their national immunisation programme. In 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). We report on the impact of PCV on invasive pneumococcal disease (IPD) incidence, clinical syndromes and patient outcomes. Methods: Pneumococcal isolates of hospitalised IPD patients between June 2004 and May 2018 were obtained from nine sentinel laboratories, covering 25% of the Dutch population. All isolates were serotyped. IPD incidence and clinical outcome were determined before and after introduction of PCV7 and after the switch to PCV10, stratified by age and serotype. Results: Compared to before PCV7 introduction, significant declines in IPD incidence were observed in 2016–2018 in children <5 years (69%), 18–49 year olds (31%) and ≥65 year olds (19%). Compared to before PCV10 introduction, the IPD incidence in 2016–2018 declined in children <5 years (RR:0.68, 95%CI:0.42–1.11), 5–17 year olds (RR:0.58, 95%CI:0.29–1.14) and 18–49 year olds (RR:0.72, 95%CI:0.57–0.90), but not in 50–64 year olds (RR:0.94, 95%CI:0.81–1.10) and ≥65 year olds (RR:1.04, 95%CI:0.0.93–1.15). While the case fatality rate (CFR) decreased from 16.2% pre-PCV to 13.4% post-PCV10 (RR:0.83, 95%CI:0.70–0.99), the switch to PCV10 had no further impact on CFR (RR:1.14, 95%CI:0.96–1.36). Conclusion: Twelve years of PCV in the Netherlands has resulted in a sustained reduction of IPD incidence in children and younger adults. The switch from PCV7 to PCV10 did not have additional impact on the IPD incidence in older adults and CFR due to emerging non-vaccine serotypes

Twelve years of pneumococcal conjugate vaccination in the Netherlands: Impact on incidence and clinical outcomes of invasive pneumococcal disease.

Introduction: In 2006, the Netherlands introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in their national immunisation programme. In 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). We report on the impact of PCV on invasive pneumococcal disease (IPD) incidence, clinical syndromes and patient outcomes. Methods: Pneumococcal isolates of hospitalised IPD patients between June 2004 and May 2018 were obtained from nine sentinel laboratories, covering 25% of the Dutch population. All isolates were serotyped. IPD incidence and clinical outcome were determined before and after introduction of PCV7 and after the switch to PCV10, stratified by age and serotype. Results: Compared to before PCV7 introduction, significant declines in IPD incidence were observed in 2016–2018 in children <5 years (69%), 18–49 year olds (31%) and ≥65 year olds (19%). Compared to before PCV10 introduction, the IPD incidence in 2016–2018 declined in children <5 years (RR:0.68, 95%CI:0.42–1.11), 5–17 year olds (RR:0.58, 95%CI:0.29–1.14) and 18–49 year olds (RR:0.72, 95%CI:0.57–0.90), but not in 50–64 year olds (RR:0.94, 95%CI:0.81–1.10) and ≥65 year olds (RR:1.04, 95%CI:0.0.93–1.15). While the case fatality rate (CFR) decreased from 16.2% pre-PCV to 13.4% post-PCV10 (RR:0.83, 95%CI:0.70–0.99), the switch to PCV10 had no further impact on CFR (RR:1.14, 95%CI:0.96–1.36). Conclusion: Twelve years of PCV in the Netherlands has resulted in a sustained reduction of IPD incidence in children and younger adults. The switch from PCV7 to PCV10 did not have additional impact on the IPD incidence in older adults and CFR due to emerging non-vaccine serotypes

Course of SP-D, YKL-40, CCL18 and CA 15-3 in adult patients hospitalised with community-acquired pneumonia and their association with disease severity and aetiology : A post-hoc analysis

BACKGROUND AND AIM: SP-D, YKL-40, CCL18 and CA 15-3 are pulmonary markers that have been extensively investigated in different chronic pulmonary diseases. However, in acute pulmonary diseases, such as community-acquired pneumonia (CAP), little is known about the course of these markers and their relationship with the aetiological agent. The aim of this study was to investigate the course of these four markers in CAP and to study influence of disease severity, aetiology and antibiotic use prior to admission on their course. METHODS: We included 291 adult patients hospitalised with CAP and 20 healthy controls. Measurements were performed in serum of day 0, 2, and 4, and at least 30 days after admission. RESULTS: Our most important results were: 1) At all time-points, including 30 days after admission, YKL-40 and CCL18 levels were higher in CAP patients compared to healthy controls; and 2) Patients with CAP caused by an intracellular, atypical bacterium had lower YKL-40 and especially CCL18 levels on and during admission in comparison with other or unknown CAP aetiology. CONCLUSIONS: Our findings suggest that these pulmonary markers could be useful to assess CAP severity and, especially YKL-40 and CCL18 by helping predict CAP caused by atypical pathogens

Inter-hospital variation in the utilization of diagnostics and their proportionality in the management of adult community-acquired pneumonia

Background: Utilization of diagnostics and biomarkers are the second largest cost drivers in the management of patients hospitalized with community-acquired pneumonia (CAP). The present study aimed to systematically assess the inter-hospital variation in these cost drivers in relation to antibiotic use in CAP. Methods: Detailed resource utilization data from 300 patients who participated in a multicenter placebo-controlled trial investigating dexamethasone as adjunctive treatment for community-acquired pneumonia was grouped into 3 categories: clinical chemistry testing, radiological exams, and microbiological testing. Based on the identified top 5 items per category, average costs were calculated per category and per hospital. Antibiotic de-escalation at day 3 and secondary ICU admission were assessed as outcomes for proportionality of diagnostics use. Results: The mean costs for diagnostics varied between hospitals from 350 (SD 31) to 841 (SD 37) euro per patient (p < 0.001). This difference was primarily explained by variation in costs for microbiological testing (mean 195 vs. 726 euro per patient, p < 0.001). There was no difference in number of secondary ICU admissions but there was an inverse association between the costs of microbiological testing and level of antibiotic de-escalation. De-escalation occurred most frequently in the hospital with the lowest cost for microbiological testing (48% vs. 30%; p = 0.018). The latter hospital had an automated physician alert system in place to consider a timely iv-to-oral switch of antibiotics. Conclusions: Large inter-hospital variation exists in resource utilization, mainly in microbiological diagnostics in the management of adult patients with community-acquired pneumonia. A counterintuitive inverse association between the magnitude of these costs and the amount of antibiotic de-escalation was found. Future studies about the optimal cost-effective set of microbiological testing for antimicrobial stewardship in pneumonia patients should acknowledge the interaction between testing, way of communication of results and triggered physician alert systems. Trial registration: ClinicalTrials.gov NCT01743755